Medical Specialties Commons^™

Investigating The Use Of Finerenone In Children With Chronic Kidney Disease And Proteinuria: Design Of The Fiona And Open-Label Extension Studies., Franz Schaefer, Giovanni Montini, Hee Gyung Kang, Johan Vande Walle, Joshua Zaritsky, Michiel F. Schreuder, Mieczyslaw Litwin, Andrea Scalise, Helen Scott, James Potts, Pablo Iveli, Stefanie Breitenstein, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria.

OBJECTIVE: FIONA and the associated open-label extension (OLE) study aim to demonstrate that …

Tobacco Exposure In Adults And Children With Proteinuric Glomerulopathies: A Neptune Cohort Study., Linda Wang, Bayle Smith-Salzberg, Kevin Ec Meyers, Dorey A. Glenn, Katherine R. Tuttle, Vimal K. Derebail, Tammy M. Brady, Keisha Gibson, Abigail R. Smith, Michelle M. O'Shaughnessy, Tarak Srivastava, Gentzon Hall, Jarcy Zee, Markus Bitzer, Christine B. Sethna

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Tobacco exposure has been recognized as a risk factor for cardiovascular disease (CVD) and progression of kidney disease. Patients with proteinuric glomerulopathies are at increased risk for cardiovascular morbidity and mortality. Multiple studies have linked tobacco exposure to CVD and chronic kidney disease, but the relationships between smoking and proteinuric glomerulopathies in adults and children have not been previously explored.

METHODS: Data from the Nephrotic Syndrome Study Network (NEPTUNE), a multi-center prospective observational study of participants with proteinuric glomerulopathies, was analyzed. 371 adults and 192 children enrolled in NEPTUNE were included in the analysis. Self-reported tobacco exposure was classified …

Nutritional Management Of The Infant With Chronic Kidney Disease Stages 2-5 And On Dialysis., Vanessa Shaw, Caroline Anderson, An Desloovere, Larry A. Greenbaum, Dieter Haffner, Christina L. Nelms, Fabio Paglialonga, Nonnie Polderman, Leila Qizalbash, José Renken-Terhaerdt, Stella Stabouli, Jetta Tuokkola, Johan Vande Walle, Bradley A. Warady, Rukshana Shroff

Manuscripts, Articles, Book Chapters and Other Papers

The nutritional management of children with chronic kidney disease (CKD) is of prime importance in meeting the challenge of maintaining normal growth and development in this population. The objective of this review is to integrate the Pediatric Renal Nutrition Taskforce clinical practice recommendations for children with CKD stages 2-5 and on dialysis, as they relate to the infant from full term birth up to 1 year of age, for healthcare professionals, including dietitians, physicians, and nurses. It addresses nutritional assessment, energy and protein requirements, delivery of the nutritional prescription, and necessary dietary modifications in the case of abnormal serum levels …

A Review Of Ferric Citrate Clinical Studies, And The Rationale And Design Of The Ferric Citrate And Chronic Kidney Disease In Children (Fit4kid) Trial., Mark R. Hanudel, Marciana L. Laster, Anthony A. Portale, Aditi Dokras, Raymond P. Quigley, German A Lozano Guzman, Joshua J. Zaritsky, Nicole A. Hayde, Frederick J. Kaskel, Mark M. Mitsnefes, Jorge A. Ramirez, Peace D. Imani, Poyyapakkam R. Srivaths, Amy J. Kogon, Michelle R. Denburg, Tom D. Blydt-Hansen, Loretta Z. Reyes, Larry A. Greenbaum, Darcy K. Weidemann, Bradley A. Warady, David A. Elashoff, Susan R. Mendley, Tamara Isakova, Isidro B. Salusky

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes. Reducing FGF23 levels in CKD may be accomplished by targeting two key stimuli of FGF23 production-dietary phosphate absorption and iron deficiency. Ferric citrate is approved for use …

Covid-19 In Solid Organ Transplantation: Disease Severity And Clinical Update., Akanksha Arya, Michael Li, Nana Aburjania, Pooja Singh, Tricia. Royer, Sean Moss, Katherine A. Belden

Department of Medicine Faculty Papers

BACKGROUND: Solid organ transplant (SOT) recipients are a complex, immunocompromised population in whom greater coronavirus disease 2019 (COVID-19) mortality has been reported compared with the general population.

METHODS: We examined a retrospective cohort of 58 SOT recipients with first-wave COVID-19, comparing patients with severe and nonsevere illness. Additionally, SOT recipients are compared with general patients with first-wave COVID-19.

RESULTS: Organs transplanted included 38 kidneys, 8 livers, 5 hearts, and 3 pancreases. Average SOT recipient age was 57.4 years; 62% were male; 46.6% were African American 36.2% were white. Comorbidities included hypertension (86%), chronic kidney disease (86%), diabetes mellitus (50%), coronary …

Childhood Kidney Disease: A Troubling Prognosis?, Darcy K. Weidemann, Bradley A. Warady, Susan L. Furth

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Duet: A Phase 2 Study Evaluating The Efficacy And Safety Of Sparsentan In Patients With Fsgs., Howard Trachtman, Peter Nelson, Sharon Adler, Kirk N. Campbell, Abanti Chaudhuri, Vimal Kumar Derebail, Giovanni Gambaro, Loreto Gesualdo, Debbie S. Gipson, Jonathan Hogan, Kenneth Lieberman, Brad Marder, Kevin Edward Meyers, Esmat Mustafa, Jai Radhakrishnan, Tarak Srivastava, Miganush Stepanians, Vladimír Tesar, Olga Zhdanova, Radko Komers, Duet Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: We evaluated and compared the effects of sparsentan, a dual endothelin type A (ETA) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS.

METHODS: In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 years with biopsy-proven FSGS, eGFR>30 ml/min per 1.73 m2, and urinary protein-to-creatinine ratio (UP/C) ≥1.0 g/g received sparsentan (200, 400, or 800 …

Recurrence Of Nephrotic Syndrome Following Kidney Transplantation Is Associated With Initial Native Kidney Biopsy Findings., Jonathan H. Pelletier, Karan R. Kumar, Rachel Engen, Adam Bensimhon, Jennifer D. Varner, Michelle N. Rheault, Tarak Srivastava, Caroline Straatmann, Cynthia Silva, T Keefe Davis, Scott E. Wenderfer, Keisha Gibson, David Selewski, John Barcia, Patricia Weng, Christoph Licht, Natasha Jawa, Mahmoud Kallash, John W. Foreman, Delbert R. Wigfall, Annabelle N. Chua, Eileen Chambers, Christoph P. Hornik, Eileen D. Brewer, Shashi K. Nagaraj, Larry A. Greenbaum, Rasheed A. Gbadegesin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end-stage kidney disease in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation and factors that predict response to immunosuppression following recurrence.

METHODS: Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006 and 12/2015. Demographics, clinical course, and biopsy data were …

An Eqtl Landscape Of Kidney Tissue In Human Nephrotic Syndrome., Christopher E. Gillies, Rosemary Putler, Rajasree Menon, Edgar Otto, Kalyn Yasutake, Viji Nair, Paul Hoover, David Lieb, Shuqiang Li, Sean Eddy, Damian Fermin, Michelle T. Mcnulty, Nephrotic Syndrome Study Network (Neptune), Nir Hacohen, Krzysztof Kiryluk, Matthias Kretzler, Xiaoquan Wen, Matthew G. Sampson, Tarak Srivastava

Manuscripts, Articles, Book Chapters and Other Papers

Expression quantitative trait loci (eQTL) studies illuminate the genetics of gene expression and, in disease research, can be particularly illuminating when using the tissues directly impacted by the condition. In nephrology, there is a paucity of eQTL studies of human kidney. Here, we used whole-genome sequencing (WGS) and microdissected glomerular (GLOM) and tubulointerstitial (TI) transcriptomes from 187 individuals with nephrotic syndrome (NS) to describe the eQTL landscape in these functionally distinct kidney structures. Using MatrixEQTL, we performed cis-eQTL analysis on GLOM (n = 136) and TI (n = 166). We used the Bayesian "Deterministic Approximation of Posteriors" (DAP) to fine-map …

Idiopathic Nodular Glomerulosclerosis In A Chronic Marijuana User; A Case Report And Review Of The Literature, Mehri Mollaee, Tibor Fülöp, Sohil Abdul Salim, Seyed Mehrdad Hamrahian

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Nodular glomerulosclerosis is a characteristic histological finding of diabetic nephropathy (DN) with thickened glomerular basement membrane (GBM) and hyalinized arterioles. Idiopathic nodular glomerulosclerosis (ING), a rare distinct clinicopathologic entity, is the term used to denote classic DN confirmed by light microscopy, immuno-fluorescence, and electron microscopy in the absence of diabetes mellitus (DM). ING has been linked to heavy tobacco smoking, chronic hypertension, obesity and insulin resistance. Its association with marijuana use is unknown. Case Presentation: We report a case of biopsy-proved ING in the absence of pre-existing history of DM and heavy smoking. This report addresses the possible accentuation …

Blood Pressure And Visit-To-Visit Blood Pressure Variability Among Individuals With Primary Proteinuric Glomerulopathies., Christine B. Sethna, Kevin E C Meyers, Laura H. Mariani, Kevin J. Psoter, Crystal A. Gadegbeku, Keisha L. Gibson, Tarak Srivastava, Matthias Kretzler, Tammy M. Brady

Manuscripts, Articles, Book Chapters and Other Papers

Hypertension and blood pressure variability (BPV; SD and average real variability) in primary proteinuric glomerulopathies are not well described. Data were from 433 participants in the NEPTUNE (Nephrotic Syndrome Study Network). Hypertensive BP status was defined as previous history of hypertension or BP ≥140/90 mm Hg for adults/≥95th percentile for children at baseline. BPV was measured in participants with ≥3 visits in the first year. Two-hundred ninety-six adults (43 years [interquartile range, 32-57.8 years], 61.5% male) and 147 children (11 years [interquartile range, 5-14 years], 57.8% male) were evaluated. At baseline, 64.8% of adults and 46.9% of children were hypertensive. …

Higher Mineralized Bone Volume Is Associated With A Lower Plain X-Ray Vascular Calcification Score In Hemodialysis Patients, Teresa Adragao, Anibal Ferreira, Joao M. Frazao, Ana Luisa Papoila, Iola Pinto, Marie-Claude Monier-Faugere, Hartmut H. Malluche

Internal Medicine Faculty Publications

Background and objectives

In dialysis patients, there is an increasing evidence that altered bone metabolism is associated with cardiovascular calcifications. The main objective of this study was to analyse, in hemodialysis patients, the relationships between bone turnover, mineralization and volume, evaluated in bone biopsies, with a plain X-ray vascular calcification score.

Design, setting, participants and measurements

In a cross-sectional study, bone biopsies and evaluation of vascular calcifications were performed in fifty hemodialysis patients. Cancellous bone volume, mineralized bone volume, osteoid volume, activation frequency, bone formation rate/bone surface, osteoid thickness and mineralization lag time were determined by histomorphometry. Vascular calcifications were …

Diet And Polycystic Kidney Disease: A Pilot Intervention Study., Jacob M. Taylor, Jill M. Hamilton-Reeves, Debra K. Sullivan, Cheryl A. Gibson, Catherine Creed, Susan E. Carlson, Donald E. Wesson, Jared J. Grantham

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND & AIMS: Dietary sodium, protein, acid precursors, and water have been linked to cyst growth in polycystic kidney disease; yet, no studies in patients have examined the feasibility of using a dietary intervention that controls all of these factors. The aim of this study was to determine if a diet, appropriate for persons of most ages, reduces the excretion of sodium, urea, acid, and decreases mean urine osmolality while gaining acceptance by patients with autosomal dominant polycystic kidney disease (ADPKD).

METHODS: Twelve adults with ADPKD enrolled in a pre-post pilot feasibility study and served as their own controls. Individuals …

Magic Study: Aims, Design And Methods Using Systemchange™ To Improve Immunosuppressive Medication Adherence In Adult Kidney Transplant Recipients., Cynthia L. Russell, Shirley Moore, Donna Hathaway, An-Lin Cheng, Guoqing Chen, Kathy Goggin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Among adult kidney transplant recipients, non-adherence to immunosuppressive medications is the leading predictor of poor outcomes, including rejection, kidney loss, and death. An alarming one-third of kidney transplant patients experience medication non-adherence even though the problem is preventable. Existing adherence interventions have proven marginally effective for those with acute and chronic illnesses and ineffective for adult kidney transplant recipients. Our purpose is to describe the design and methods of the MAGIC (Medication Adherence Given Individual SystemCHANGE™) trial

METHODS/DESIGN: We report the design of a randomized controlled trial with an attention-control group to test an innovative 6-month SystemCHANGE™ intervention designed …

Membranoproliferative Glomerulonephritis Recurrence After Kidney Transplantation: Using The New Classification., Sami Alasfar, Naima Carter-Monroe, Avi Z Rosenberg, Robert A Montgomery, Nada Alachkar

Pathology Faculty Publications

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is an uncommon glomerular disorder that may lead to end stage renal disease (ESRD). With new understanding of the disease pathogenesis, the classical classification as MPGN types I, II, III has changed. Data on post-transplant MPGN, in particular with the newly refined classification, is limited. We present our center's experience of MPGN after kidney transplantation using the new classification.

METHODS: This is a retrospective study of 34 patients with ESRD due to MPGN who received 40 kidney transplants between 1994 and 2014. We reviewed the available biopsies' data using the new classification. We assessed post transplantation …

Efficacy Of Galactose And Adalimumab In Patients With Resistant Focal Segmental Glomerulosclerosis: Report Of The Font Clinical Trial Group., Howard Trachtman, Suzanne Vento, Emily Herreshoff, Milena Radeva, Jennifer Gassman, Daniel T. Stein, Virginia J. Savin, Mukut Sharma, Jochen Reiser, Changli Wei, Michael Somers, Tarak Srivastava, Debbie S. Gipson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Patients with resistant focal segmental glomerulosclerosis (FSGS) who are unresponsive to corticosteroids and other immunosuppressive agents are at very high risk of progression to end stage kidney disease. In the absence of curative treatment, current therapy centers on renoprotective interventions that reduce proteinuria and fibrosis. The FONT (Novel Therapies for Resistant FSGS) Phase II clinical trial (NCT00814255, Registration date December 22, 2008) was designed to assess the efficacy of adalimumab and galactose compared to standard medical therapy which was comprised of lisinopril, losartan, and atorvastatin.

METHODS: Key eligibility criteria were biopsy confirmed primary FSGS or documentation of a causative …

The Adipose Tissue Production Of Adiponectin Is Increased In End-Stage Renal Disease., Maria P Martinez Cantarin, Scott A Waldman, Cataldo Doria, Adam M Frank, Warren R Maley, Carlo B Ramirez, Scott W Keith, Bonita Falkner

Department of Medicine Faculty Papers

Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared with 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis …

Renal Function And Proteinuria After Successful Immunosuppressive Therapies In Patients With Fsgs., Ronald J. Hogg, Aaron Friedman, Tom Greene, Milena Radeva, Milos N. Budisavljevic, Jennifer Gassman, Debbie S. Gipson, J Ashley Jefferson, Eunice G. John, Frederick J. Kaskel, Asha Moudgil, Marva Moxey-Mims, Luis A. Ortiz, Jeffrey R. Schelling, William Schnaper, Tarak Srivastava, Howard Trachtman, V Matti Vehaskari, Craig Wong, Robert P. Woronieki, Scott K. Van Why, Anna Zolotnitskaya

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: In the FSGS Clinical Trial, 22 cyclosporine-treated and 20 mycophenolate/dexamethasone-treated patients experienced a complete or partial remission after 26 weeks, completed 52 weeks of treatment, and were studied through 78 weeks. Herein, changes in the urine protein/creatinine ratio (UP/C) and estimated GFR (eGFR) throughout the entire study period are defined.

DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The FSGS Clinical Trial, which was conducted from November 2004 to January 2010, enrolled patients aged 2-40 years, with eGFR ≥40 ml/min per 1.73 m(2) and UP/C >1 mg/mg after ≥4 weeks of corticosteroid therapy. Both groups received lisinopril or losartan throughout …

A Phase I/Iia Clinical Trial Of A Recombinant Rho Protein Antagonist In Acute Spinal Cord Injury., Michael G Fehlings, Nicholas Theodore, James Harrop, Gilles Maurais, Charles Kuntz, Chris I Shaffrey, Brian K Kwon, Jens Chapman, Albert Yee, Allyson Tighe, Lisa Mckerracher

Department of Neurosurgery Faculty Papers

Multiple lines of evidence have validated the Rho pathway as important in controlling the neuronal response to growth inhibitory proteins after central nervous system (CNS) injury. A drug called BA-210 (trademarked as Cethrin(®)) blocks activation of Rho and has shown promise in pre-clinical animal studies in being used to treat spinal cord injury (SCI). This is a report of a Phase I/IIa clinical study designed to test the safety and tolerability of the drug, and the neurological status of patients following the administration of a single dose of BA-210 applied during surgery following acute SCI. Patients with thoracic (T2-T12) or …

Hypertension In Children And Adolescents: Epidemiology And Natural History., Bonita Falkner

Department of Medicine Faculty Papers

Primary hypertension is detectable in children and adolescents and, as in adults, is associated with a positive family history of hypertension, obesity, and life-style factors. Owing to the well-established childhood obesity epidemic, the population prevalence of high blood pressure (BP) in the young is increasing. Hypertension in childhood is commonly associated with other cardiovascular risk factors as well as obesity. Although death and cardiovascular disability do not occur in hypertensive children, intermediate markers of target organ damage, such as left ventricular hypertrophy, thickening of the carotid vessel wall, retinal vascular changes, and even subtle cognitive changes, are detectable in children …